There are several studies within this project. However, the largest of these is the Agricultural Health Study (AHS). This prospective cohort study was designed to evaluate the relationship between pesticides and other agricultural factors and the risk of cancer and other diseases. Enrollment in this study includes about 90,000 men and women from Iowa and North Carolina. From 1993-1997 detailed information was obtained by self-administered questionnaire and from 1998 through September 2003 and again from 2004 through 2010 computer assisted telephone interviews updated the information collected at enrollment. Telephone interviews include questions on pesticides used and other agricultural exposures, lifestyle factors, medical and family history of disease, and diet. A questionnaire focused on chronic disease other than cancer was administered in 2010-2015 and focused on chronic disease other than cancer was led by investigators from NIEHS. The AHS has provided information on a number of pesticide-cancer associations over the years. In this FY, several papers were published, including one on bladder cancer, showing a link between aromatic amine pesticides and bladder cancer risk in the pesticide applicators. Another evaluation showed an increased association between metolachlor use and liver cancer, which had been previously linked to liver cancer in rodents. The AHS spouses represent an important population in which to evaluate lower exposure levels, as well as cancer among women. A study among this group showed an increased risk of thyroid and ovarian cancers with exposure to specific organophosphate insecticides. Buccal cells are available from approximately 50% of the cohort, and provides a source of genomic DNA for GXE studies and studies of epigenetic mechanisms. Smaller sub-studies have biological specimens for the evaluation of intermediate effects of exposure and outcome. This year a study was published evaluating the association between telomere length and a number of pesticides and showed an association between 2,4-D use and shorter telomeres. There is currently an effort underway to recruit 1,600 farmers within the AHS to update exposure information and collect blood and other biological specimens, and dust for the purpose of evaluating several hypotheses related to pesticide exposure. A paper describing the methodology and preliminary statistics was published this year. The AHS has been a productive study with which to evaluate many hypotheses related to pesticides. However, early life exposures and future cancer risk are of great interest. At enrollment, AHS participants provided information on their offspring. A new effort was launched to enumerate these offspring and follow them with the purpose of evaluating their early life pesticide and other farm exposures and future cancer risk. The AHS also contributes data to AGRICOH, the consortium of agricultural cohorts. An initial paper describing the harmonization of exposure across studies was published this year, with etiologic results focused on lymphohematopoietic malignancies to follow. Pooled studies of breast and prostate cancer have also been initiated within the consortium. Other studies within the Branch are also evaluating risks associated with pesticide exposure. A pooled study of case-control studies of multiple myeloma demonstrated an increased risk associated with the use of DDT, carbaryl and captan. maternal occupational exposure to agricultural chemicals may increase the risk of giving birth to a child with limb defects.